Self-wettable solid phase extraction medium

ABSTRACT

A functionalized macroporous poly(styrene divinylbenzene) particle comprises at least one ionic functional group covalently bonded thereto, the functionalized particle having sorptive capability towards an analyte, said functional group being present in the range of 0.1 to 2.5 milliequivalents per gram of poly(styrene divinylbenzene). The functionalized particles can be used in a packed column or enmeshed in a nonwoven web for utility in solid phase extraction applications.

This is a division of application No. 08/238,364 filed May 5, 1994.

FIELD OF THE INVENTION

This invention relates to particles useful for solid phase extraction(SPE) processes, which particles have been partially chemically modifiedunder controlled conditions to optimize sorptive properties. In anotheraspect, there are disclosed methods of making the particles and usingthe particles in packed columns and in composite sheet-like articles ofthe invention.

BACKGROUND OF THE INVENTION

Classical methods for separating analytes from water and other fluidsuse liquid/liquid extraction (LLE) procedures wherein the analyte ispreferentially partitioned from an aqueous based liquid into animmiscible extraction liquid phase. Efficiency and selectivity ofextraction of specific analytes by LLE is dependent on the partitioncoefficient of the analyte between the two liquids and is limited by thetype of extraction liquid that can be used. Recently, solid phaseextraction (SPE) procedures have been developed using solid particulatephases which can interact with the analyte by ion exchange, chelation,covalent bond formation, size exclusion, sorption, and other mechanismsto bind and remove the analyte from the fluid. SPE processes aredescribed in Analytica Chimica Acta, 236, 157-164 (1990) and LC/GC, 9:5,332-337 (1991). Application of mixed-mode SPE using copolymerizedmixed-mode resins where C₁₈ (octadecyl) and sulfonic acid functionalgroups are in closer proximity than on "blended" mixed mode resins isreported in J. Chrom. 629 (1993) 11-21.

The type of SPE particulate chosen to effect separation of specificanalytes can be inorganic, inorganic with organic coatings, inorganicwith covalently bonded organic functional groups, polymeric organicresins and derivatives thereof.

U.S. Pat. No. 4,895,662 describes a process for purification of aqueouseffluent from bleaching of wood pulp using macroporous adsorbent resinshaving been post-crosslinked in the swollen state and functionalizedwith hydrophilic groups prior to contact with the waste effluent.

U.S. Pat. Nos. 5,104,545 and 5,135,656 describe a process for removingwater soluble metal salts of organic acids from oil field water usingnonionogenic macroreticular adsorption resins such as XAD-16™ from Rohmand Haas Co., Philadelphia, Pa.

U.S. Pat. Nos. 5,071,565 and 5,230,806 describe neutral functionalizedresins which take up organics by adsorption rather than ion exchange andteach that the amount of functional group relative to the amount ofpoly(styrene divinylbenzene) is not critical. They teach that thefunctional group must be neutral since anionic or cationic resins maypick up undesirable materials that are present. Utility of these resinsfor SPE of phenols was reported by J. S. Fritz et al. in J. Chrom. 641(1993) 57-61.

U.S. Pat. No. 5,114,591 describes ion exchange resins for reducingorganic material content of paint booth waste water having functionalgroups that provide ion exchange activity and also adsorb neutralmolecules in varying degrees.

U.S. Pat. No. 5,236,594 describes a process for removing specifictoxicants containing at least one carboxylate group from aqueouspetroleum waste streams using non-ionic macroreticular polymeric resins.

U.S. Pat. No. 4,537,683 describes anion exchange particles alone oranion exchange particles combined with cation exchange particles in theform of a floc. It is reported that the level of ion exchangefunctionality has only a limited effect on the particles' ability toremove trihalomethane precursors.

U.S. Pat. No. 5,279,742 describes solid phase extraction media andmethods using sorptive particulate in particulate loaded PTFE matrixsheet configurations wherein disks of the same or different compositionscan be stacked to achieve separations.

A major requirement for particulate useful for SPE is that it hassufficient sorptive capacity to retain the analyte of interest. Theretention characteristics of a specific analyte by a sorptiveparticulate is expressed numerically as its "capacity factor (k')", see"Contemporary Practice of Chromatography", C. F. Poole and S. A.Schuette, Elsevier, New York, N.Y. (1984) pp 2-6.

J. J. Sun and J. S. Fritz in J. Chrom. 522 (1990) 95-105 describechemical modifications of polymeric resins to increase analyte capacityfactor (k') for high performance liquid chromatography applications.

SUMMARY OF THE INVENTION

Briefly, the present invention provides a functionalized macroporouspoly(styrene divinylbenzene) particle comprising ionic (cationic oranionic) functional groups covalently bonded thereto, the functionalizedparticle having sorptive capability towards an analyte, the functionalgroup being present in a concentration range of 0.1 to 2.5milliequivalents per gram of functionalized poly(styrenedivinylbenzene).

Preferably, the functionalized particle exhibits a maximum range inretentive capacity for selected analytes dependent on the level offunctional (i.e., substituted) group present.

Preferably, the analyte exhibits a maximum value of capacity factor (k')using functionalized poly(styrene divinylbenzene) particles in thespecified exchange concentration range compared to a lesser value ofcapacity factor (k') for the same analyte for similarly functionalizedparticles present in an amount outside the ion exchange concentrationrange. Surprisingly, the maximum in retentive capacity is not coincidentwith the maximum possible concentration of the functional group. Theparticles are useful in solid phase extraction applications, both whenpacked in columns and when incorporated in fibrous membranes.

In another aspect, the functionalized particles of the inventioncomprising cationic or anionic functional groups in the ion exchangeconcentration range designated above, exhibit superior wettingproperties towards liquids, preferably aqueous-based liquids, comparedto functionalized particles comprising functional groups outside thedesignated ion exchange concentration range. Aqueous-based liquidsinclude water, optionally in combination with at least one of miscibleorganic liquids and inorganic species.

In a further aspect, the solid phase extraction particles of theinvention can be packed in a column or bed, or the particles can beincorporated into a porous fibrous membrane to provide a porous fibrousmedium in sheet form, and one or a stack of such media can be useful inapplications in separations science.

In yet another aspect, the present invention provides a method ofoptimizing sorptive properties wherein the capacity factor (k') of ananalyte to be sorbed by functionalized poly(styrene divinylbenzene)particulate is maximized, the method comprising the step of providing apoly(styrene divinylbenzene) particle having covalently bonded theretoin the ion exchange concentration range of 0.1 to 2.5 milliequivalentsof cationic or anionic functional groups per gram of functionalizedpolymer. The analyte exhibits a maximum in capacity factor (k') withrespect to poly(styrene divinylbenzene) functionalized in the specifiedconcentration range compared to (k') of the same analyte for similarlyfunctionalized poly(styrene divinylbenzene) outside the designatedconcentration range.

In another aspect, the invention relates to a method of removing ananalyte in a concentrated form from a solution by contacting thefunctionalized particle of the invention with the analyte for a time andat a temperature sufficient to bind the analyte to the particle. In afurther step of the method, the invention relates to regenerating thefunctionalized particle by removing the analyte in a concentrated formfrom the functionalized particle, preferably by eluting the analyte witha suitable solvent.

Functionalized particles are prepared from macroporous poly(styrenedivinylbenzene) particulates, which are commercially available (see, forexample, U.S. Pat. Nos. 4,501,826, 4,382,124, 4,297,220, 4,256,840, and4,224,415), and the functionalization is achieved by methods known inthe art.

It is believed to be novel in the art that controlled levels of chemicalalteration (functionalization) of sorptive particulate can provideoptimum analyte retentive capacity and optimum wetting capability forparticles used in solid phase extractions.

In this application:

"analyte" means the molecular species being isolated;

"capacity factor" (k') means a numerical measure of the retentioncharacteristics of a specific analyte by a sorptive particulate(stationary phase). It is defined as the ratio of the time spent by theanalyte in the stationary phase to the time it spends in the mobilephase as expressed in Equation 1:

    Equation 1: k'=(t.sub.r -t.sub.m)/t.sub.m

where t_(r) is the analyte retention time in a column and t_(m) is thecolumn dead time or the time of passage through the column of anunretained species; (k') varies with particle size, surface area,chemical functionality of the sorbent particulate, and composition ofthe mobile phase;

"degree of derivatization", "ion exchange capacity", and "capacity" areused interchangeably;

"derivative of" or "derivatized" or "functionalized" poly(styrenedivinylbenzene) means poly(styrene divinylbenzene) having covalentlybonded thereto at least one functional group which accepts protons ordonates protons, which accepts electrons or donates electrons, or whichshares electrons;

"hydrophilic" means having an affinity for, attracting, adsorbing, orabsorbing water; preferably it means having a surface polarity of 0.5 orgreater;

"hydrophobic" means lacking an affinity for, repelling, or failing toadsorb or absorb water; preferably it means having a low surfacepolarity, for example, in the range of 0.1 to less than 0.5;

"macroporous resin" also known as "macroreticular resin", means a memberof a class of highly crosslinked polymer particles penetrated bychannels through which solutions can diffuse; often used as ionexchangers. Pores are regions between densely packed polymer chains.Pores less than 50 Angstrom are referred to as micropores, pores between50 to 200 Angstroms are referred to as mesopores, and pores greater than200 Angstrom are referred to as macropores;

"nonpolar compound" means molecules which have no permanent electricdipole moment;

"normal phase system" means a process using a more polar stationaryphase with a less polar moving phase to effect separation of molecularspecies;

"particle" or "particulate" means a regular or irregular shapedparticle, having an average size in the range of 0.1 to 150 micrometers,preferably in the range of 1 to 30 micrometers, and more preferably inthe range of 5 to 20 micrometers; also included is polymeric fiber pulphaving a length in the range of 0.8 mm to 4.0 mm and an average diameterin the range of less than 1 to 20 μm;

"polar compound" means molecules which contain polar covalent bonds;they can ionize when dissolved; polar compounds include inorganic acids,bases, and salts;

"reversed phase system" means a process using a less polar stationaryphase with a more polar moving phase to effect separation of molecularspecies;

"solid phase extraction" (SPE) means a process employing a solid phasefor isolating classes of molecular species from fluid phases such asgases and liquids by sorption, ion exchange, chelation, size exclusion(molecular filtration), affinity, ion pairing, etc. mechanisms;

"sorptive" or "sorption" or "sorbent" means capable of taking up andholding by either absorption or adsorption;

"wettability" means the ability of any solid surface to be wetted whenin contact with a liquid; that is, the surface tension of the liquid isreduced so that the liquid spreads over the surface; and

"wetting" means treatment of hydrophobic particulate or medium with anorganic solvent, usually methanol, to provide higher polarity to thesurface making it more accessible to high surface tension fluids such aswater.

One problem encountered in the prior art is that hydrophobic sorptiveparticulate in packed columns or in particle loaded web composites usedfor SPE of hydrophobic analytes in water require a preliminary "wetting"step with solvents such as methanol. Wetting is necessary because thelow surface energy of the hydrophobic particles or composite does notallow high surface tension aqueous solutions efficient access to thehigh surface area of the sorptive particles' internal pores.

A number of approaches have been evaluated to increase the wettabilityor hydrophilicity of these particles and composites. One approach toeliminating or minimizing the wetting problem can be the addition ofhydrophilic adjuvants such as micro-crystalline cellulose fibers tocomposite sheet articles comprising polytetrafluoroethylene polymer(PTFE) or other hydrophobic fibrils and various sorptive particulate, asdescribed in U.S. Pat. No. 4,810,381. While this approach increases theoverall hydrophilic character of the composite, it does not addresswetting of the internal pores of entrapped sorptive particulate.Intramolecular introduction of hydrophilic groups, for example, on themacroporous poly(styrene divinylbenzene) resin particles of theinvention provide "self wettability" of both external surfaces andavailable internal pore surfaces.

No prior art of which we are aware discloses that controlling the levelsof-ionic (cationic or anionic) chemical modification of poly(styrenedivinylbenzene) taught by the instant invention can provide optimizedcapacity factor (k') for separations. There is no prior art evidence tosuggest that specific concentration levels of functionalization ofhydrophobic particles with hydrophilic groups will provide optimum SPEproperties especially with respect to non-ionic neutral analytes.Indeed, intuition would lead one of ordinary skill in the art to believethat more functionalization is better. Surprisingly, the presentinvention shows that improved separations are realized atless-than-complete functionalizations/concentrations. While it isappreciated in the art that substitution of particles with hydrophilicgroups improves particle wettability, it is an advance in the art tocontrol the concentration of the hydrophilic groups to provide optimumwettability and analyte capacity factor (k').

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a series of four plots of phenol capacity factor (k') vs. ionexchange capacity of sulfonated poly(styrene divinylbenzene) resins.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION

The functionalized particles of the invention can be prepared frompoly(styrene divinylbenzene) particles. Particularly preferredparticulate are:

    ______________________________________                                                  Average                                                                       Particle                Available                                   Material  size       Trademark    from                                        ______________________________________                                        highly cross-                                                                           50-100     Amberchrom ™                                                                            Supelco, Inc.                               linked styrene                                                                          micrometers                                                                              CG-161 m     Bellefonte,                                 and divinyl-                      PA                                          benzene co-                                                                   polymers, high                                                                performance                                                                   material*                                                                     highly cross-                                                                           220-830    Amberlite ™                                                                             Supelco, Inc.                               linked styrene                                                                          micrometers                                                                              XAD-2        Bellefonte,                                 and divinyl-                                                                            (ground to              PA                                          benzene   average size                                                        copolymer*                                                                              about 50                                                                      micrometers)                                                        highly cross-                                                                           5-20                    Phenomenex,                                 linked styrene                                                                          micrometers             Inc.,                                       and divinyl-                      Torrance,                                   benzene                           CA                                          copolymer*                        Sarasep,                                                                      Santa Clara,                                                                  CA;                                                                           Polymer                                                                       Laboratories,                                                                 Amherst, MA;                                                                  Hamilton Co.,                                                                 Reno, NV                                    ______________________________________                                         *Disclosed in one or more of U.S. Pat. Nos. 4,501,826, 4,382,124,             4,297,220, 4,256,840, 4,224,415                                          

The functionalized poly(styrene divinylbenzene) particles can be cationor anion exchange particles. Strong cation exchangers include theparticles functionalized by, for example, strong acid sulfonate (HSO₃)groups which are anionic; weak cation exchangers include the particlesfunctionalized by, for example, carboxylate (COOH) groups which areanionic. Other functionalized poly(styrene divinylbenzene) particles canbe strong anion exchangers which include the base particlesfunctionalized by, for example, quaternary ammonium groups N⁺ (R)₃wherein each R independently can be C₁ to C₄ alkyl groups. Weak anionexchangers include aminated groups N(R¹)₂ wherein each R¹ independentlycan be hydrogen, or C₁ to C₄ alkyl or alkanol groups. RepresentativeN(R¹)₂ groups include NH₂, N(C₂ H₅)₂, N(CH₃)₂, and N(C₂ H₄ OH)₂, all ofwhich are cationic.

In a preferred embodiment, the invention relates to poly(styrenedivinylbenzene) particles which have been functionalized (i.e.,chemically altered) by the addition of optimum levels of sulfonic acidgroups to at least one of ortho and para positions on the aromatic ringstructure of the resin. Ring substitution by functional groups occurs inaccordance with known rules of organic chemistry, see for example Carl.R. Noller, "Textbook of Organic Chemistry" W. B. Saunders Company,Philadelphia, Pa. (1951) pp. 331-351. The functionalized particle can beprepared from the base particle which is mixed with glacial acetic acidand then reacted with concentrated sulfuric acid. The reaction can bequenched with water when the desired degree of sulfonation is achieved.Details of this method are disclosed in Example 1, below.

It has been found that functionalization of the particles in the ionexchange concentration range of 0.1 to 2.5 milliequivalents ofcovalently bonded ionic functionality per gram of functionalizedpolymer, preferably in the range of 0.15 to 2.0, more preferably in therange of 0.2 to 1.1 milliequivalents per gram, and most preferably inthe ion exchange concentration range of 0.3 to less than 0.9milliequivalents per gram and even more preferred 0.3 to 0.8, and thevery most preferred about 0.3 to 0.6 milliequivalents per gram providesmaximum retentivity of polar or semi-polar analytes in solid phaseextractions.

In one embodiment, the range of sulfonate chemical modification levelsto improve particle wettability coincides with analyte capacity factor(k') enhancement to an optimum level of 0.6 milliequivalents per grambut further increased levels of sulfonate group substitution resulted indecreasing numerical values of the analyte capacity factor as shown inFIG. 1. This range of functionalization also provides optimization ofwetting characteristics of the particles. In SPE, the sulfonatefunctionalized particles can be effective in the absence of a wettingagent.

In a second embodiment, carboxylate functional poly(styrenedivinylbenzene) can be prepared for use in solid phase extractions. Inone method, poly(styrene divinylbenzene) resin particles can bechemically altered by oxidation of pendant groups such as aromatic vinylor aromatic alkyl groups to form carboxylate functional groups. Suchoxidation can be performed as is known in the art, using, for example,oxidizing agents such as sodium hypochlorite, potassium permanganate, ordilute nitric acid, in amounts so as to control the level of conversionto carboxylate groups. See, for example, Lee, Donald G., "The oxidationof organic compounds by permanganate ion and hexavalent chromium" OpenCourt Publishing Company: La Salle, Ill., 1980, p. 43-64, and J. March,"Advanced Organic Chemistry 3rd Ed.", Wiley-Interscience: New York,1985. In a second method, varying levels of carboxylate functionalitycan be obtained by copolymerization of styrene, divinylbenzene, and asuitable carboxylic acid functional monomer such as methacrylic acid.This second method has been described by R. Kunin in "Ion ExchangeResins" 2nd edition, Wiley: New York, (1958), p. 87, and by Meitzner etal., U.S. Pat. No. 4,256,840.

The ability of organic resins to sorb certain analyte molecules whichare moderately water-soluble may be directly related to thehydrophilic/hydrophobic nature of the particulate. In the preferredembodiment, the hydrophilicity of poly(styrene divinylbenzene)particulate increases as more SO₃ ⁻ substitution occurs but the effecton capacity factor (k') is surprising because sulfonation above about0.6 milli-equivalent/gram results in a decrease in the capacity factor,(k'). Optimization of capacity factor (k') in the prior art involvedchoosing among various functionalized particulate. This inventionteaches modification of the adsorptive character of a given particulateby controlled functionalization of the particulate with appropriatelevels of certain functional groups.

Any of the particulate material may have a spherical shape, a regularshape or an irregular shape. Particulate material which has been founduseful in the invention has an average size within the range of 0.1 toabout 150 micrometers, preferably in the range of 0.1 to 100micrometers, more preferably 1 to 100 micrometers, and most preferably 5to 20 micrometers. It has been found advantageous in some instances toemploy particulate materials in two or more particle size ranges fallingwithin the broad range. As an example, particles of the presentinvention having an average size in the range of 0.1-30 micrometershaving solid phase extraction capability may be employed in combinationwith particles having an average size in the range 1 to 150 micrometersacting as a property modifier. Larger particulate (e.g., 40 to 150micrometers, even up to 4 mm or higher for industrial applications) areparticularly desirable for packed columns and some nonwoven webs,particularly those disclosed in U.S. Ser. No. 07/929,985, now allowed asU.S. Pat. No. 5,328,758.

As noted above, more than one type of functionalized poly(styrenedivinylbenzene) particulate can be useful in columns and membranes ofthe present invention. The functionalized particles can be pre-mixed inany proportion; the total functionalized SPE particles of this inventioncan be present in the range of more than 20 up to 100 weight percent ofthe total particles, preferably 35 to 100 weight percent, morepreferably 50 to 100 weight percent organic polymeric particles, mostpreferably 90 to 100 weight percent derivatized organic polymericparticles of this invention, and 0 to 80 weight percent of totalparticulate of any other SPE particles, preferably 0 to 65 weightpercent, and more preferably 0 to 50 weight percent, and most preferably0 to 10 weight percent of other SPE particles. Other SPE particlesinclude porous organic-coated or uncoated particles, and porous organicpolymeric particles which can be functionalized or unfunctionalized.

In another aspect, the present invention provides an improved SPEcomposite structure and method therefor, the composite structurepreferably being a uniformly porous composite sheet comprising sorptiveparticles of the invention distributed uniformly throughout a fibrousmatrix formed of nonwoven fibers. In such a structure almost all of theparticles are separate one from another and are entrapped in a matrix offibers that restrains the particle. The preferred sheet of the inventionhas a thickness in the range of 125 to 10,000 micrometers. The ratio oftotal particles to fibrous matrix is in the range of 40:1 to 1:4,preferably 19:1 to 4:1, by weight.

In particle-loaded composite articles of the invention, propertymodifiers and adjuvants may be advantageously added to the primaryparticulate material in the fibrous medium to provide furtherimprovement in or modification of properties. For example, modifierparticulate can include inactive materials such as low surface areaglass beads to act as property modifiers and processing aids. Coloringor fluorescing particulate can be added at low levels (up to 10 weightpercent of particulate) to aid in visualizing sample components to beseparated. Chemically active particulate adjuvants which indicatechemical activity or acidity of the sample components can be useful fordiagnostic purposes.

When the present invention particles are incorporated intoparticle-loaded fibrous articles, which preferably are microfibrousarticles, the articles comprise in the range of 20 to 80 volume percentfibers and particulate, preferably 40 to 60 volume percent fibers andparticulate, and 80 to 20 volume percent air, preferably 60 to 40 volumepercent air.

Fibrous matrices useful for incorporation of the particulate of theinvention include nonwoven webs, such as nonwoven polymeric websincluding polytetrafluoroethylene (PTFE), polyolefins such aspolyethylene or polypropylene, polyaramid (e.g., Kevlar™, Dupont),polyamides such as nylon 6 and nylon 66, polyurethanes, polyesters suchas polyethylene terephthalate, polyacrylonitrile (Cyanamid, Wayne,N.J.); other nonwoven webs include glass fiber webs and ceramic fiberwebs.

PTFE provides a particularly useful fibrillated matrix for the presentinvention derivatized particulates. The composite article can beprepared, for example, by the methods disclosed in any of U.S. Pat. Nos.4,810,381, 4,985,296, 5,071,610, 5,279,743, and 4,985,296.

Other webs useful for incorporating particles of the present inventioninclude nonwoven macro- and microfibrous webs such as melt-blown webs,spunbonded or air-laid webs, blown fibrous webs, as disclosed in U.S.Ser. No. 07/929,985, now allowed as U.S. Pat. No. 5,328,758, which isincorporated herein by reference for making and using such webs.Pressing or fusing of the webs is generally not required in the articlesof the present invention. Also useful can be glass fiber or ceramicfiber webs.

The particulate-containing fibrous webs of the invention can be usefulin a first mode wherein the composite article of the invention is usedfor preconcentration and isolation of certain materials for furtheranalysis by, for example, high resolution column chromatography. In thismode, which is well known in the art and commonly called solid phaseextraction, solvent and sample flow are introduced at an angle of about90 degrees to the surface of the sheet. This is a conventionalconfiguration and the separation path length is equal to the thicknessof the sheet. The path length can be increased by stacking additionallayers (media) which may be the same or of different composition but theindividual layers need not be intimately bound together. This mode iseffective for one step or multi-step adsorption-desorption separations.This mode is effective using sorptive ion exchange particulate in thenormal or reverse phase modes. The article strongly adsorbs the analyteof interest onto the active particulate in the composite and undesirablecomponents are washed out with a first eluant. Conversely, undesirablecomponents can be strongly bound and the analyte can be washed out withthe first eluant. A more effective eluting solvent is then used todisplace the desired component from the particulate allowing it to berecovered in a more concentrated and unified form.

The composite extraction articles of the invention can be of a varietyof sizes and shapes. Preferably the articles can be sheet-like materialswhich, for example, can be in disk or strip form.

This invention discloses a solid phase extraction (SPE) disk/sheetcomposite material and a method which is effective, for example, inisolating polar, semi-polar, and nonpolar organic contaminants fromfluids (gases and liquids). The article can be used as a singleself-supporting sheet, or a combination of sheets to form a stack, or asa composite film adhered to supports, such as glass, paper, metals, orpolymers. The article is preferred for polar and semi-polar analytes. Inparticular, residues of explosives, phenolic compounds, and organicacids are common contaminants of solids, air, and water, and can beefficiently removed, concentrated, or isolated using the teachings ofthe present invention. The isolations can be performed on an analyticalscale or in large scale applications.

Analytes which are nonpolar, i.e., minimal dipole moment, arehydrophobic and usually exhibit high capacity factor (k') levels withhydrophobic sorptive particles such as C₁₈ bonded silica and neutralmacroporous resins such as poly(styrene divinylbenzene). Using thefunctionalized particles of the present invention, these non-polaranalytes are not expected to exhibit substantial increases in (k')values compared to those (k') increases found for polar and semipolaranalytes. Some elevation of capacity factor (k') can occur due toincreased surface area available from access to wetted internal pores.

Representative polar and semi-polar compounds (analytes) which can besorbed by the functionalized particles of the present invention includeexplosives such as 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane (HMX),explosive impurities such as dinitrotoluene, and phenolic compounds suchas phenol, 2-chlorophenol, 4-chlorophenol, o- or p-cresol, 2- or4-nitrophenol, 4,6-dinitro-o-cresol, 2,4-dinitrophenol,2,4-dimethylphenol, 4-chloro-3-methylphenol, 2-methyl-4,6-dinitrophenol,pentachlorophenol, 2,4-dichlorophenol, 2,4,5-trichlorophenol, and2,4,6-trichlorophenol, and catechol, which are pollutants in water andwhich are of environmental concern. Representative pesticides, generallyconsidered semi-polar compounds, which can be recovered from aqueousliquids include atrazine, alachlor, and diazinon. Representative drugs,generally considered semi-polar compounds, include d-amphetamine,methamphetamine, salicylate, ibuprofen, butalbital, acetaminophen,amobarbital, pentobarbital, secobarbital, glutethimide, phencyclidine(PCP), phenobarbital, naproxyn, methadone, methaqualone, propoxyphene,cocaine, imipramine, desipramine, phenytoin, codeine, morphine, andflurazepam.

Neutral analytes such as ethyl pyruvate and butanedione exhibit amaximum capacity factor within the concentration range of the invention.These compounds are commonly extracted from water using liquid/liquidextractions (LLE), described in EPA Method 608, 625, etc. It is highlydesirable to replace liquid-liquid extraction (LLE) methods with solidphase extraction (SPE) materials and methodology to reduce or eliminateextraction solvent usage, extraction time, and environmental hazards.This aspect of the invention discloses using a hybrid of column particleand membrane technologies to provide a means of overcoming thedeficiencies of conventional methods with substantial savings in timeand cost.

It has been found advantageous where combinations of contaminants are tobe extracted to use a stack of disks (e.g., 2 to 5 or more) with one ormore types of particulate chosen, each having optimum extraction orreaction efficiency for individual contaminants. Choice of elutionsolvents depends on contaminants and extraction particulate.

This invention is useful in the extraction of inorganic and organicsubstances from liquids and gases in a flow-through or filtration mode.The invention can be used on an analytical scale, as in the testing ofwater samples for environmental pollutants. This invention can also beused on a larger scale as in the remedial removal of contaminants oranalytes from liquid or gas sources.

After use, the article can be recycled by simply eluting the sorbedpollutants from the article using a liquid capable of removing thesorbed materials from the sorbent. Heat or supercritical fluiddisplacement or elution of the sorbed analyte can also be used.

Particles which can be loaded in a packed column and composite articlesof the invention have utility in a wide variety of separations whereinthe choice of the particulate material is useful for size controlledfiltration or steric exclusion, for simple one step or multistepsorption-desorption separations of specific components, for applicationswhere sorptive particulate perform chemical or biochemical separations,for ion-exchange conversions of cations and anions, for purification ofmaterials, and for chromatographic separations and analyses in bothpassive and forced flow modes, for hydrophobic reverse phase and normalphase chromatography, all being processes which are known to thoseskilled in the art.

Objects and advantages of this invention are further illustrated by thefollowing examples, but the particular materials and amounts thereofrecited in these examples, as well as other conditions and details,should not be construed to unduly limit this invention.

EXAMPLES Example 1 Chemical Modification of Poly(styrene Divinylbenzene)

A first procedure utilized 2 gram portions of 8 micrometer poly(styrenedivinylbenzene) (SDVB) resin particulate from Sarasep, Santa Clara,Calif. Eight resin samples were each mixed with 2 milliliters of glacialacetic acid to form a slurry. Concentrated sulfuric acid was addedsequentially in fifty milliliter portions to each of these slurries andallowed to react at different temperatures and for different times. Thereactions were then quenched by dilution of the sulfuric acid in themixture with water and the resin particles were separated by filtration.After washing with water and drying, the degree of sulfonation of eachsample was determined by titration with a standard solution of sodiumhydroxide to determine ion exchange capacity in milliequivalents pergram. Reaction times, temperatures, and exchange capacity inmilliequivalents per gram are listed for these samples in Table 1.

                  TABLE 1                                                         ______________________________________                                        Sulfonation levels of poly(styrene divinylbenzene)                                                            Ion                                                     Reaction              Exchange                                                Time       Temperature                                                                              Capacity                                      Sample No.                                                                              (minutes)  (degrees C)                                                                              (meq./gm)                                     ______________________________________                                        1         --         --         0.0                                           (comparative a)                                                               2         0.5        0          0.1                                           3         2          0          0.4                                           4         4          0          0.6                                           5         10         25         1.0                                           6         20         25         1.2                                           7         90         25         1.5                                           8         90         50         2.1                                           9         90         85         2.7                                           (comparative b)                                                               ______________________________________                                    

Sample 1 (comparative a) was unfunctionalized poly(styrenedivinylbenzene) starting material and Sample 9 (comparative b)represented a typical strong cation exchange resin which had beenheavily sulfonated (ion exchange capacity outside the present inventionconcentration range).

A second procedure for chemically modifying poly(styrene divinylbenzene)comprised mixing 5 ml of glacial acetic acid and 5 ml of concentrated H₂SO₄ with a sample of the base resin. A 60-minute reaction at roomtemperature produced a dark orange resin, but it was not wettable.Finally a reaction time of 5-10 minutes was used with heating (100°-150°C.). These resins were dark brown and wettable by aqueous solutions. Thefinal resin with a capacity of 0.7 meq S₃ ⁻ /g was made by the followingconditions:

Two g. of macroporous poly(styrene divinylbenzene) resin (Sarasep, Inc.)were dried with gentle heat (100° C. for 5-10 minutes). Glacial aceticacid (5 mL) was added and the mixture was placed in an oil bath at 150°C. Concentrated H₂ SO₄ (5 mL) was added and the mixture was vigorouslystirred with a cross-shaped magnetic bar for 5 minutes. The reaction wasquenched by pouring the mixture into 100 mL of cool H₂ O. The aqueousmixture was filtered and rinsed with successive 100 mL portions ofdeionized water, acetone, and methanol. The functionalized polymericresin was then dried at approximately 100° C. for several hours.

The resin was pre-wetted with methanol and then solid phase extractionof several phenols was performed with this resin (50 mg of resinparticles packed in a small SPE column (20 mm×2.1 mm ID). Each phenolwas present in 15 mL of H₂ O. After SPE was performed, each phenol waseluted with 1 mL of methanol. Recoveries (average of three trials) arelisted below in Table 2.

                  TABLE 2                                                         ______________________________________                                        SPE of Phenols Using Sulfonated Resin                                         Compound        Percent Recovery                                              ______________________________________                                        phenol           95%                                                          2-chlorophenol  96                                                            4-chlorophenol  93                                                            p-cresol        92                                                            2,3-dichlorophenol                                                                            82                                                            ______________________________________                                    

Example 2 Capacity Factor (k') vs Ion Exchange Capacity

Samples 1 through 9 listed in Table 1 were packed into a column toevaluate the effect of various levels of sulfonation of the poly(styrenedivinylbenzene) on sorptive capacity. A series of relatively hydrophiliccompounds including phenol, catechol, ethyl pyruvate (a neutral ester),and 2,3-butanedione (a neutral ketone) were then passed through thecolumn without methanol pre-wetting to determine capacity factors (k').Data obtained is listed in Table 3.

                  TABLE 3                                                         ______________________________________                                        Analyte Capacity Factors with                                                 Unwetted Particles                                                                             Capacity Factor (k')                                                                  Cate-  Ethyl  Butane-                                Sample                                                                              Capacity*  Phenol  chol   pyruvate                                                                             dione                                  ______________________________________                                        1     0.0        21      1      0      1                                            (compara-                                                                     tive)                                                                   2     0.1        40      1      0      0                                      3     0.4        272     34     40     3                                      4     0.6        436     60     60     12                                     5     1.0        315     59     54     8                                      6     1.2        290     56     38     7                                      7     1.5        183     38     26     6                                      8     2.1        80      16     9      3                                      9     2.7        47      10     5      2                                            (compara-                                                                     tive)                                                                   ______________________________________                                         *SO.sub.3 .sup.-  ion exchange capacity in milliequivalents/gram from         Table 1.                                                                 

Example 3 Capacity Factor (k') vs Ion Exchange Capacity

Examination of data in Table 3 shows that the capacity factor (k') ineach case reached a maximum value when the ion exchange capacity wasabout 0.6 milliequivalents per gram. A second trial was performed usingthe particulate wetting procedure described by Hagen et al., AnalyticaChimica Acta, 236 (1990) 157-164, and the results are shown in Table 4.

                  TABLE 4                                                         ______________________________________                                        Analyte Capacity Factors With Wetted* Particles                                     Ion        Capacity Factor (k')                                               Exchange           Cate-  Ethyl  Butane-                                Sample                                                                              Capacity** Phenol  chol   pyruvate                                                                             dione                                  ______________________________________                                        1     0.0        49      10     0      1                                            (compara-                                                                     tive)                                                                   2     0.1        124     32     4      2                                      3     0.4        350     45     49     4                                      4     0.6        457     90     79     14                                     5     1.0        381     70     55     8                                      6     1.2        324     78     57     7                                      7     1.5        209     45     34     6                                      8     2.1        127     25     16     4                                      9     2.7        55      12     6      2                                      ______________________________________                                         *particulate wetted with methanol                                             **SO.sub.3 .sup.-  ion exchange capacity in milliequivalents/gram        

Examination of data in Tables 3 and 4 show that the capacity factor (k')for the ester, ketone and phenolics in each case reached a maximum valuewhen the ion exchange capacity was about 0.6 milli-equivalents per gramof particulate.

FIG. 1 illustrates graphically the optimization of the capacity factor(k') by controlling the degree of sulfonation of the particulate.

It is important to note that the unfunctionalized particulate gives alow value for the capacity factor (k'). The poly(styrene divinylbenzene)particulate that was more highly sulfonated and is typical of a cationexchange resin of prior art also gave a low value for the capacityfactor (k'). The maximum capacity factor (k') value occurred at about0.6 milliequivalents/gram for the sulfonated particle but can vary forother functional groups such as the acetyl or hydroxyl groups whichincrease wettability.

More particularly, in the Drawing, FIG. 1 shows four plots from data ofTable 6 of phenol capacity factor (k') vs. ion exchange capacity ofpoly(styrene divinylbenzene) resins. More specifically, in each run theparticles were 5-8 micrometer average diameter and were packed in acolumn 20 mm×2.1 mm ID. Plot A shows data of a run using methanol wettedsulfonated poly(styrene divinylbenzene) particles (sample 4 of Table 1);plot B shows data of a run using non-wetted sulfonated poly(styrenedivinylbenzene) particles (sample 4 of Table 1); plot C shows data of arun using a mixture (sample 10b of Table 6) of sulfonated poly(styrenedivinylbenzene) particles (sample 9 of Table 1) and unfunctionalizedpoly(styrene divinylbenzene) particles (sample 1, Table 1), theparticles having been wetted with methanol before the run; plot D showsdata of a run using a mixture of non-wetted sulfonated poly(styrenedivinylbenzene) particles (sample 9 of Table 1) and unfunctionalizedpoly(styrene divinylbenzene) particles (sample 1, Table 1). Plots A, B,C, and D show that there is a maximum capacity factor (k') achieved whenthe ion exchange capacity of the derivatized poly(styrenedivinylbenzene) is in the range of 0.1 to 2.5 milliequivalents,preferably 0.15 to 2.0 milliequivalents per gram, and more preferably0.2 to 1.1 milliequivalents. For wetted and non-wetted particles, thereis a maximum capacity for phenol achieved when the ion exchange capacityof the functionalized poly(styrene divinylbenzene) is in the range of0.1 to 2.5 milliequivalents per gram of functionalized poly(styrenedivinylbenzene), preferably 1.5 to 2.0 and most preferably 0.2 to 1.1milliequivalents per gram. Wetted particles provide optimal capacityfactor (k') of functionalized poly(styrene divinylbenzene) particles. Asshown by plots C and D, a mixture of functionalized andnon-functionalized particles provided very little increased capacityfactor (k') with increase in ion exchange capacity, although the wettedparticles showed some benefit in capacity factor (k') compared tO amixture of non-wetted particles.

Example 4

PTFE composite membranes comprising 80% of sample 4 sulfonatedpoly(styrene divinylbenzene) (0.6 meq/gm ion exchange capacity) and 20%by weight PTFE were evaluated for their ability to extract a series ofphenolic compounds listed in Table 5 below. The recoveries obtained werecompared to those obtained for PTFE composite membranes comprising 20weight percent PTFE and 80 weight percent AmberChrome 71 resin, whichwas disclosed in U.S. Pat. No. 5,279,742, as a desirable sorptiveparticle. One hundred parts per billion by weight of each phenol wereprepared in a 500 milliliter volume of deionized water. The pH wasadjusted to 2.0 with HCl and 10% by weight NaCl was added to help saltout the soluble phenols from the aqueous phase to the sorptive solidphase. This procedure is well known in the art. Lowering the pH assuresthat the phenols are protonated for better transfer to the hydrophobicSPE media.

The water sample containing the phenolic analytes was pulled through theSPE membrane (47 mm diameter) using a standard filtration apparatus(Millipore Corp., Bedford, Mass.) with water aspirator vacuum of 66 cm(26 incheS) of Hg. After the extraction step, the phenolic analytes wereeluted from the membrane with 3 successive 3 mL aliquots oftetrahydrofuran (THF). The 3 aliquots were combined and THF was added togive a final volume of 10 milliliters for analysis by liquidchromatography. The analytical results listed in Table 5 are an averageof 4 determinations for the sulfonated poly(styrene divinylbenzene) and3 determinations for the AmberChrom 71.

                  TABLE 5                                                         ______________________________________                                        Recovery Data for the SPE of Phenols                                                         Percent Recovery                                                              Sulfonated poly                                                               (styrene divinyl-                                                             benzene)                                                       Compound       (0.6 meq/gm) AmberChrom 71                                     ______________________________________                                        phenol         79.0         9.6                                               4-nitrophenol  94.7         27.2                                              2,4-dinitrophenol                                                                            85.4         26.9                                              2-nitrophenol  65.8         16.7                                              2,4-dimethylphenol                                                                           72.4         20.7                                              4-chloro-3-methylphenol                                                                      85.1         28.7                                              2-methyl-4,6-dinitrophenol                                                                   79.5         33.6                                              2,4,6-trichlorophenol                                                                        75.9         30.0                                              pentachlorophenol                                                                            96.1         37.2                                              ______________________________________                                    

The data show the recoveries obtained for the sulfonated poly(styrenedivinylbenzene) were considered very good for these phenols compared tothose obtainable using a conventional sorptive particulate, AmberChrom71.

Example 5

Capacity factor (k') for phenol versus degree of sulfonation ofpoly(styrene divinylbenzene) sorbent

Data in Table 6 (which contains data of Tables 3 and 4, columns 1-3 forsamples 1-9) show that an optimum capacity factor (k') can be achievedby controlled functionalization of the poly(styrene divinylbenzene)polymer particles. In additional trials, simple mixtures of theun-sulfonated (neutral) particles and heavily sulfonated particles(strong cation exchange) as illustrated by samples 10a, 10b, and 10c didnot achieve optimization of the capacity factor (k') as shown by samples1-9.

                  TABLE 6                                                         ______________________________________                                        Capacity factor (k') for                                                      phenol vs. degree of sulfonation of                                           poly(styrene divinylbenzene) sorbent                                                   Ion Exchange                                                                  Capacity      CH.sub.3 OH                                            Sample   (meq. SO.sub.3.sup.- /                                                                      Wetted   Non-wetted                                    number   gm)           (k')     (k')                                          ______________________________________                                        1.sup.(a)                                                                              0.0           49       21                                            2        0.1           124      40                                            3        0.4           350      272                                           4        0.6           457      436                                           5        1.0           381      315                                           6        1.2           324      290                                           7        1.5           209      183                                           8        2.1           127      80                                            9.sup.(a)                                                                              2.7           55       47                                            10a*.sup.(a)                                                                           0.0           50       21                                            10b**    0.6           56       33                                            10c*.sup.(a)                                                                           2.7           53       47                                            ______________________________________                                         .sup.(a) comparative                                                          *second trial of samples 1 and 9 respectively to compare (k') of mixtures     **mixture of portions of samples 10a and 10c give sample 10b with a net       ion exchange capacity of 0.6 meq SO.sub.3.sup.- /gm                      

Example 6

A. Samples of macroporous poly(styrene divinylbenzene) resins withvarious concentrations of carboxylic acid functionality (a weak cationexchange group) were prepared as described by R. Kunin in "Ion ExchangeResins", 2nd edition, Wiley:New York, (1958) p. 87, and by Meitzner etal. in U.S. Pat. No. 4,256,840 wherein the ion exchange capacities werevaried by changing the ratio of methacrylic acid, divinylbenzene andstyrene starting monomers. These samples with ion exchange capacitiesranging from 0 for non-carboxylated base poly(styrene divinylbenzene),to 0.3, 2.9, and 5.8 milliequivalents per gram for carboxylated resins,were incorporated into 0.5 mm thick PTFE sheet material comprising 20percent PTFE and 80 percent by weight of each resin particulate using aprocess described in U.S. Pat. No. 5,147,539. Forty seven millimeterdiameter disks were cut from these sheet materials and the particleloaded disks comprising particles with varying ion exchange capacitieswere individually tested for SPE efficiency using the phenolic analyteslisted in Table 5.

In these trials, 500 milliliter test samples containing a mixture of 100parts per billion (100 μg per liter) of each phenolic analyte indistilled water were adjusted to a pH of 2 with hydrochloric acid.(Acidification is often used to suppress ionization and keep thephenolic analyte in the protonated form to enhance extractability byreverse phase particulate.) Samples were pulled through the disksmounted in a standard Millipore™ filtration apparatus using a vacuum of66 cm (26 inches) Hg. Phenolic analytes adsorbed from these watersamples by the resin loaded disks were subsequently desorbed i.e.,eluted from the disks using 2 sequential 10 milliliter portions oftetrahydrofuran (THF) which were then combined and brought to 25milliliter analytical volumes with THF. These eluant solutions wereanalyzed by liquid chromatography to measure the phenolic analytecontent to determine the percent recovery obtained by the SPE process.The data is shown in Table 7A, below.

                                      TABLE 7A                                    __________________________________________________________________________    Percent Recovery of Phenols vs Ion Exchange Capacity of Carboxylated SDB      Copolymer Resin                                                               Exchange                       4-chloro,                                      Capacity  4-nitro                                                                           2,4-dinitro                                                                         2-nitro                                                                           2,4-dimethyl                                                                         3-methyl                                                                           2,4-dichloro                                                                         2,4,6-trichloro                                                                       pentachloro                (meq/gm)                                                                            phenol                                                                            phenol                                                                            phenol                                                                              phenol                                                                            phenol phenol                                                                             phenol phenol  phenol                     __________________________________________________________________________    0*    7.0 37.0                                                                              105.4†                                                                       104.1†                                                                     108.3†                                                                        85.6 91.9   102.1†                                                                         93.2                       0.3   16.4                                                                              94.1                                                                              99.7  98.0                                                                              104.9†                                                                        83.2 89.7   96.8    91.8                       2.9   12.5                                                                              60.5                                                                              89.0  90.1                                                                              92.0   73.9 83.8   91.1    94.8                       5.8   10.1                                                                              45.6                                                                              78.5  93.4                                                                              87.2   80.2 91.9   102.1†                                                                         93.2                       Average %                                                                           13.4                                                                              3.0 2.6   2.7 4.0    5.4  4.3    4.6     3.6                        RSD**                                                                         __________________________________________________________________________     *represents comparative sample of unfunctionalized poly(styrene               divinylbenzene)                                                               **relative standard deviation                                                 † recoveries above 100% represent experimental scatter            

Data in Table 7A indicate that good recoveries were found for the lesspolar phenolics tested (i.e., 2-nitrophenol, 2,4-dimethyl phenol,4-chloro-3-methyl phenol, 2,4,6-trichlorophenol, and pentachlorophenol)with little dependence on the level of carboxyl groups present on thepoly(styrene divinylbenzene)sorbent. Better recoveries were obtained forthe more polar phenolic analytes (phenol and 4-nitrophenol). Inparticular, phenol and 4-nitrophenol exhibited a definite maximumpercent recovery with the resin sample which had 0.3 milli-equivalentsper gram ion exchange capacity level of carboxylate group. Recoverylevels for 4-nitrophenol subsequently decreased when higher levels ofcarboxyl groups were present. Recoveries of the 2-nitrophenol isomerwere consistently high regardless of the level of carboxylate groupsubstitution. This is not unexpected since the close proximity of thenitro and phenol groups favors intramolecular hydrogen bonding andresults in decreasing water solubility. The 2,4-dinitrophenol analyterecoveries were higher than those found for 4-nitrophenol but alsodecreased with increasing levels of carboxylate substitution of thesorptive resin particulate.

B. In another set of trials, a series of partially carboxylatedcopolymer resin particulates were prepared via the method as describedby Kunin (see Example 6A) using various levels of methacrylic acidmonomer. These resin particles were incorporated into PTFE membranescomprising 80 weight percent particles and 20 weight percent PTFE asdescribed above. The resulting composite articles were evaluated forsorptive properties using polar probe compound analytes; phenol,4-nitrophenol, and neutral probe analytes: dimethyl phthalate (DMP),diethyl phthalate (DEP), dibutyl phthalate (DBP), dioctyl phthalate(DOP), and o-methyl anisole (OMA) (an ether). Experimental procedure wasthe same as for Table 7A, except that the analytes were present at 5parts per million (5 mg per liter) and methanol was present at twopercent by volume due to sample preparation procedures. The data ofTable 7B show the percent recoveries obtained. Maxima occurred at thelevel of 0.3 milliequivalent carboxylate functionality per gram ofcopolymer resin for phenol and 4-nitrophenol. The phenol and4-nitrophenol analytes are polar and showed low capacity factors (k')which gave lower percent recovery levels using the poly(styrenedivinylbenzene) copolymer resin based particles. The phthalate estersand o-methyl anisole are neutral analytes and had high capacity factors(k') as shown by the near 100 percent recovery levels, and no effect onrecovery levels was observed with different levels of carboxylatefunctionality.

                                      TABLE 7B                                    __________________________________________________________________________    Percent Recovery vs. Ion Exchange Capacity of                                 Carboxylated Poly(styrene divinylbenzene) Copolymer Resin                     Exchange                                                                      Capacity                                                                      meq/cm  phenol                                                                            4-nitrophenol                                                                        DMP DEP DBP DOP OMA                                        __________________________________________________________________________    1 0.0   3.4 13.2   99.6                                                                              99.3                                                                              98.4                                                                              98.6                                                                              96.8                                       2 0.3   4.8 19.8   100.6                                                                             99.8                                                                              99.1                                                                              98.1                                                                              96.9                                       3 0.6   3.5 14.3   100.0                                                                             99.2                                                                              98.7                                                                              98.2                                                                              96.2                                       4 0.9   3.3 14.4   100.0                                                                             99.6                                                                              98.9                                                                              98.3                                                                              96.6                                       5 1.5   4.1 16.3   99.3                                                                              99.3                                                                              98.0                                                                              97.4                                                                              95.8                                       __________________________________________________________________________

It is recognized in the art that analyte capacity factor (k') values aredirectly proportional to analyte recovery levels in SPE processes. Dataof Tables 7A and 7B show that controlling the level of carboxylfunctionality on poly(styrene divinylbenzene) copolymer resin can beused to maximize extractability of certain analytes.

Example 7 Comprehensive Serum and Urine Drug Screens

Disks comprising 20 percent PTFE and 80 percent sample number 4 fromTable 3, Example 2 (poly(styrene divinylbenzene) particulatefunctionalized with sulfonate functional group at an ion exchangecapacity of 0.6 meq/gm) were tested in a comprehensive drug screeningprocedure. The results were compared with data obtained using diskscomprising 20 percent PTFE and 80 percent Clean Screen™ (CS) particulatefrom United Chemical Technology, Bristol, Pa. (commercially availablesilica based particles coated with a mixed phase comprising an octylreverse phase group and a strong cation exchange functionality). Resultswere also compared with data obtained using TOXI-TUBEs for acidic andbasic drug extractions from urine, commercially available from Toxi-Lab,Inc., Irvine, Calif.

Materials and Methods

Drug Standards

Stock standard solution used was 100 μg/mL of each of the followingdrugs in methanol:

    ______________________________________                                        d-amphetamine         naproxyn                                                methamphetamine       methadone                                               salicylate            methaqualone                                            ibuprofen             propoxyphene                                            butalbital            cocaine                                                 acetaminophen         imipramine                                              amobarbital           desipramine                                             pentobarbital         phenytoin                                               secobarbital          codeine                                                 glutethimide          morphine                                                phencyclidine (PCP)   flurazepam                                              phenobarbital                                                                 ______________________________________                                    

Internal standard solution used was 0.5 mg/mL cyheptamide in methanol.

Extraction Procedure--Extraction Disk Cartridges (3M Co., St. Paul,Minn.), (Columns B and C in Table 8)

1. Samples were prepared as follows:

Urines: Sequentially were added 3 mL distilled water, 2 mL 0.1Mphosphate buffer (pH=6.0), and 10 μL of internal standard solution to 2mL of urine (spiked with an appropriate amount of drug standard).Samples were thoroughly shaken.

Serums: Sequentially were added 4 mL distilled water, 2 mL 0.1Mphosphate buffer (pH =6.0), and 10 μL of internal standard solution to 1mL of serum (spiked with an appropriate amount of drug standard).Samples were thoroughly shaken.

2. The extraction disk cartridge was conditioned with sequentialadditions of one 3-mL volume of methanol, one 3-mL volume of distilledwater, and one 1-mL volume of 0.1M phosphate buffer (pH=6.0). Eachaddition was aspirated but the disk was not allowed to dry.

3. Sample was applied and aspirated at full vacuum.

4. Disk cartridge was washed with one 3-mL volume of distilled waterfollowed by one 1-mL volume of 1.0M acetic acid. Disk cartridge wasdried at full vacuum for 5 minutes, then washed with one 2-mL volume ofhexane.

5. Elution of acidic and neutral drugs was accomplished using one 3-mLvolume of hexane/ethyl acetate (50/50); the eluate was collected at lessthan 5 mL/minute, then transferred into a conical bottom dry down tube.

6. The disk cartridge was washed with one 3-mL volume of methanol anddried at full vacuum for 5 minutes.

7. Basic drugs were eluted with one 2-mL volume of elution solvent (24mL methylene chloride, 6 mL isopropanol, and 0.9 mL ammonium hydroxide;made fresh daily). Eluate was transferred into the same tube as theprevious eluate.

8. The eluate sample was concentrated by drying under a gentle stream ofcompressed air without heating. When completely dry, 150 μL ofchloroform was added to the residue and the sample was thoroughly mixed.

9. Sample was analyzed by injecting 1 μL of chloroform solutioncontaining the analytes into a chromatograph.

Extraction Procedure--Liquid-Liquid Extraction for Urines (Columns D andE in Table 8)

1. Each extraction tube was prepared by adding 2 mL of urine (spikedwith an appropriate amount of drug standard) and 10 μL of internalstandard solution (described above) to TOXI-TUBEs (basic and acidicextractions).

2. Contents of each extraction tube was mixed by gentle inversion for aminimum of five minutes.

3. The tube was centrifuged at high speed for 5 minutes.

4. The organic layer was transferred to conical bottom dry down tube.

5. The sample was concentrating drying the organic layer under a gentlestream of compressed air without heating. When completely dry, 150 μL ofchloroform was added to the residue and the tube was shaken.

6. The sample was analyzed by injecting 1 μL of chloroform containingthe analytes into a chromatograph.

Extraction Procedure--Liquid-Liquid Extraction for Serum (Column A inTable 8)

Stock Solution A:

Ammonium sulfate crystals were washed twice with methanol and dried at100° C. for several hours. A supersaturated solution of the crystals wasprepared in distilled water. Twenty mL of concentrated hydrochloric acidwas then mixed with 250 mL of the supersaturated ammonium sulfatesolution.

1. Each extraction tube was prepared by adding 0.4 mL of Stock SolutionA with 10 μL of internal standard (described above), to 1 mL of serum(spiked with an appropriate amount of drug standard). Nine mL ofmethylene chloride extraction solvent were then added.

2. The tube was shaken for 5 to 10 minutes.

3. The tube was centrifuged at high speed for 5 minutes.

4. The methylene chloride layer was transferred to a conical bottom drydown tube.

5. The sample was concentrated by evaporating the methylene chlorideextraction solvent using a gentle stream of compressed air. Whencompletely dry, 150 μL of chloroform were added to the extracted residueand the sample was thoroughly mixed.

6. Analyze sample. One (1) μL of chloroform containing the analytes wasinjected into a chromatograph for analysis.

                                      TABLE 8                                     __________________________________________________________________________    Detection of Drugs from Extracted Samples                                              Serum Extractions                                                                              Urine Extractions                                            A.sup.(a)                                                                          B.sup.(a)   D        E        B                                          Liquid/                                                                            Clean C     Toxi-Tube ™.sup.(a)                                                                 Toxi-Tube ™.sup.(a)                                                                 Clean C                           Drug     Liquid                                                                             Screen ™                                                                         SCX/SDB                                                                             Basic    Acidic   Screen ™                                                                         SCX/SDB                     __________________________________________________________________________    d-amphetamine                                                                          -    +     +     -        -        +     +                           methamphetamine                                                                        -    +     +     -        -        +     +                           ibuprofen                                                                              +    -     -     -        -        -     +                           butalbital                                                                             +    +     +     +        +        +     +                           amobarbital                                                                            +    +     +     +        +        +     +                           pentobarbital                                                                          +    +     +     +        +        +     +                           secobarbital                                                                           +    +     +     +        +        +     +                           glutethimide                                                                           +    +     +     +        +        +     +                           phencyclidine                                                                          +    +     +     +        +        +     +                           phenobarbital                                                                          +    -     +     +        +        -     +                           methadone                                                                              +    +     +     +        +        +     +                           methaqualone                                                                           +    +     +     +        +        +     +                           propoxyphene                                                                           +    +     +     +        +        +     +                           cocaine  +    +     +     +        -        +     +                           imipramine                                                                             +    +     +     +        +        +     +                           desipramine                                                                            -    +     -     +        -        -     +                           phenytoin                                                                              +    +     +     +        +        +     +                           codeine  +    +     +     +        -        +     +                           morphine -    +     +     +        -        +     +                           flurazepam                                                                             +    +     +     +        -        +     +                           __________________________________________________________________________     .sup.(a) comparative                                                          A Liquid/Liquid extraction - conventional method                              B Clean Screen - particle loaded web as a disk in a cartridge format          C SCX/SDB - present invention particle loaded as web; a disk in a             cartridge                                                                     D ToxiTube Basic - (comparative) liquid/liquid extraction                     E ToxiTube Acidic - (comparative) liquid/liquid extraction               

The data of Table 8 show that the present invention particle-loadedmembranes were at least as good and in most instances better as ascreening device than conventional devices for establishing the presenceof 20 commonly tested drugs.

Advantages of sulfonated poly(styrene divinylbenzene) particles in amembrane format for comprehensive drug screening include eliminating theneed for separate basic and acidic liquid/liquid extractions, and thustwo injections for chromatographic analysis. The present inventionmembrane allows for one extraction (two elution solvents are used andcombined before dry down) and one injection for chromatographicanalysis, which saves time.

The present invention membrane allows more drugs to be detected in thescreening method when compared to conventional liquid/liquid analyses[e.g., amphetamine, methamphetamine, morphine, codeine, cocaine (serum)and amphetamine, methamphetamine, ibuprofen, phencyclidine,phenobarbitol (urine)].

The present invention membrane saves time and money in this screeningmode. Also, there is the potential for automation using the presentinvention materials. Further, the present invention provides a lowerdetection limit for drugs.

Various modifications and alterations of this invention will becomeapparent to those skilled in the art without departing from the scopeand spirit of this invention, and it should be understood that thisinvention is not to be unduly limited to the illustrative embodimentsset forth herein.

We claim:
 1. A self-wettable solid phase extraction or reaction mediumcomprising(a) a fibrous matrix, and (b) sorptive particles enmeshed insaid matrix comprising(1) in the range of more than 20 to 100 weightpercent, based on total particles, of functionalized poly(styrenedivinylbenzene) particles comprising at least one ionic functional groupselected from the group consisting of a sulfonate group, carboxylategroup, quaternary ammonium groups N⁺ (R)₃ wherein each R independentlyis selected from C₁ to C₄ alkyl groups and aminated groups N(R¹)₂wherein each R¹ is independently selected from the group consisting ofhydrogen, C₁ to C₄ alkyl groups, and C₁ to C₄ alkanol groups covalentlybonded thereto, the functionalized particles having sorptive capabilitytowards an analyte in solid phase extraction, the functional group beingpresent in a concentration range of 0.1 to 2.5 milliequivalents per gramof functionalized poly(styrene divinylbenzene), and (2) in the range of0 to less than 80 weight percent, based on total particles, of porous,organic-coated or uncoated, inorganic particles,the ratio of sorptiveparticles to fibrous matrix in said solid phase extraction or reactionmedium being in the range of 40:1 to 1:4 by weight, said mediumcomprising optimum wettability in the specified concentration range. 2.The medium according to claim 1 wherein said fibrous matrix is selectedfrom the group consisting of polytetrafluoroethylene, polyolefins,polyaramids, polyamides, polyurethanes, cellulosics, glasses, andceramics.
 3. The medium according to claim 1 wherein said ionicfunctional groups of said particle are present in the range of 0.15 to2.0 milliequivalents per gram.
 4. The medium according to claim 1wherein said ionic functional groups of said particle are present in therange of 0.2 to 1.1 milliequivalents per gram.
 5. The medium accordingto claim 1 wherein said ionic functional groups of said particle arepresent in the range of 0.3 to 0.9 milliequivalents per gram.
 6. Themedium according to claim 1 wherein said ionic functional groups of saidparticle are present in the range of 0.3 to 0.6 milliequivalents pergram.
 7. The medium according to claim 1 wherein said ionic group ofsaid particle is a sulfonate group.
 8. The medium according to claim 1wherein said ionic group of said particle is a carboxylate group.
 9. Themedium according to claim 1 wherein said ionic group of said particle isa quaternary ammonium group N⁺ (R)₃ wherein each R independently isselected from C₁ to C₄ alkyl groups.
 10. The medium according to claim 1wherein said ionic group of said particle is an aminated group N(R¹)₂wherein each R¹ is independently selected from the group consisting ofhydrogen, C₁ to C₄ alkyl groups, and C₁ to C₄ alkanol groups.
 11. Themedium according to claim 1 wherein said analyte is selected from thegroup consisting of phenolics, alcohols, ketones, ethers, and esters.12. The medium according to claim 1 wherein said analyte is selectedfrom the group consisting of explosive residues, pesticides, and drugs.13. The medium according to claim 1 wherein said particle has solidphase extraction capability.
 14. The medium according to claim 1 whereinsaid particle has an average size in the range of 0.1 to 150micrometers.
 15. The medium according to claim 1 wherein said porousfibrous matrix comprises nonwoven fibers.
 16. The medium according toclaim 15 wherein said nonwoven fibers are fibrillatedpolytetrafluoroethylene.
 17. The medium according to claim 15 whereinsaid nonwoven fibers are polyolefin fibers.
 18. The medium according toclaim 15 wherein said nonwoven fibers are selected from the groupconsisting of polyaramid, polyamide, polyurethane, polyester, andpolyacrylonitrile fibers.
 19. The medium according to claim 15 whereinsaid nonwoven fibers are selected from the group consisting of glass andceramic fibers.
 20. The medium according to claim 1 which is a disk. 21.The medium according to claim 20 wherein said disk is included in astack of disks comprising one or more types of particulates.
 22. Themedium according to claim 1 wherein said analyte is neutral.
 23. Themedium according to claim 22 wherein said analyte is non-ionic.
 24. Themedium according to claim 22 wherein said analyte is a polar organicanalyte.
 25. The medium according to claim 22 wherein said analyte is asemi-polar organic analyte.
 26. The medium according to claim 22 whereinsaid analyte is a nonpolar organic analyte.